The group-specific murine coronavirus genes are not essential, but their deletion, by reverse genetics, is

Cornelis A M de Haan1, Paul S Masters, Xiaolan Shen

  • 1Virology Division, Utrecht University, Utrecht, The Netherlands. x.haan@vet.uu.nl

Virology
|May 31, 2002
PubMed

Insights

Mouse hepatitis virus (MHV) group-specific genes are nonessential and can be deleted. Deleting these genes from MHV creates attenuated viruses, suggesting potential for live coronavirus vaccines.

Area of Science:

  • Virology
  • Molecular Biology
  • Vaccine Development

Background:

  • Coronaviruses possess essential genes for replication and structure, alongside group-specific genes with unknown functions.
  • These group-specific genes vary significantly across coronavirus groups and are unique to each.
  • The functions of coronavirus group-specific genes remain largely uncharacterized.

Purpose of the Study:

  • To investigate the significance of group-specific genes in the group 2 mouse hepatitis virus (MHV).
  • To generate recombinant MHV lacking group-specific genes to assess their necessity and function.
  • To evaluate the potential of MHV group-specific gene deletion for vaccine development.

Main Methods:

  • Utilized a novel host-switching-based targeted recombination system to delete group-specific genes from the MHV genome.
  • Created recombinant viruses with separate or combined deletions of the two group-specific gene clusters.
  • Assessed the viability of the resulting recombinant deletion mutant viruses.

Main Results:

  • All generated recombinant deletion mutant viruses were viable, indicating group-specific genes are nonessential.
  • The deletion of group-specific genes resulted in the attenuation of MHV in its natural host, the mouse.
  • MHV group-specific genes were confirmed as accessory genes.

Conclusions:

  • The group-specific genes of MHV are nonessential and can be deleted without compromising viral viability.
  • Deletion of these genes leads to viral attenuation, presenting a promising strategy for developing live attenuated coronavirus vaccines.